Deep Brain vs Vagus Nerve Stimulation for Epilepsy

(DBS-VNS-ES Trial)

Overseen By George M Ibrahim, MD, PhD

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: The Hospital for Sick Children

Must be taking: Anti-epileptics

Disqualifiers: Substance abuse, Cardiac arrhythmias, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 36-48 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores two treatments, Deep Brain Stimulation (DBS) and Vagus Nerve Stimulation (VNS), to determine which is more effective for children with drug-resistant epilepsy. It aims to assist those whose seizures do not improve with medications. Participants will receive either a DBS or VNS device surgically implanted to manage their seizures. Children with epilepsy that does not respond to at least two medications and who experience epileptic or tonic spasms might be suitable candidates for this trial. As an unphased trial, it offers a unique opportunity for children to access potentially life-changing treatments not yet widely available.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that both Deep Brain Stimulation (DBS) and Vagus Nerve Stimulation (VNS) can help reduce seizures in people with epilepsy. DBS, approved by the FDA for other conditions, has been used for years. Research indicates it can lower seizure frequency by up to 79% after two years without causing major side effects over time. VNS also has a long history of use, reducing seizures by 50-100% in about 45-65% of patients, with optimal results appearing around six months into treatment. Both treatments are generally well-tolerated, meaning most people do not experience severe side effects. These findings suggest that both DBS and VNS are safe options for managing epilepsy. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Deep Brain Stimulation (DBS) and Vagus Nerve Stimulation (VNS) for epilepsy because they offer unique approaches compared to traditional medications like antiepileptic drugs. Unlike most treatments that rely on chemicals to control seizures, DBS involves implanting electrodes in the brain to directly modulate abnormal electrical activity. VNS, on the other hand, uses a device implanted in the chest to stimulate the vagus nerve, which can help reduce seizure frequency by influencing brain networks from the outside. These methods provide alternative options for patients who don't respond well to standard drug therapies.

What evidence suggests that this trial's treatments could be effective for epilepsy?

This trial will compare Deep Brain Stimulation (DBS) with Vagus Nerve Stimulation (VNS) for treating epilepsy. Research shows that DBS can significantly reduce seizures in people with epilepsy. Studies have found that, after several years of treatment, seizures decrease by more than 60% on average. Approximately 70% of patients with hard-to-treat epilepsy respond well to DBS, experiencing more than a 50% reduction in seizure frequency.

For VNS, many studies report that 40-70% of patients see their seizures reduced by half or more. One study found that 65% of patients with medication-resistant epilepsy showed improvements in both seizure frequency and severity. Both DBS and VNS, tested in separate arms of this trial, offer hope for patients who haven't found success with other treatments. ^{1 4 6 7 8}

Who Is on the Research Team?

George M Ibrahim, MD, PhD

Principal Investigator

The Hospital for Sick Children

Are You a Good Fit for This Trial?

This trial is for children aged 5 to under 18 with drug-resistant epilepsy, specifically those experiencing epileptic and tonic spasms confirmed by EEG. Participants must be able to attend all study-related appointments for a year and have tried two anti-epileptic drugs without success. Consent from parents or guardians is required.

Inclusion Criteria

My epilepsy hasn't improved after trying two different medications.

My main seizure type is epileptic or tonic spasms, confirmed by EEG.

I am between 5 years and under 18 years old.

Exclusion Criteria

Substance dependence or abuse in the last 6 months, excluding caffeine and nicotine

Pregnancy

I cannot return to SickKids for follow-up visits.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo surgical implantation of either Vagus Nerve Stimulation (VNS) or Deep Brain Stimulation (DBS) devices

36-48 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments including quality of life and seizure severity over a 1-year period

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Deep Brain Stimulation
• Vagus Nerve Stimulation

Trial Overview The study compares Deep Brain Stimulation (DBS) with Vagus Nerve Stimulation (VNS) in treating drug-resistant epilepsy and epileptic spasms in children. It's a randomized control trial, meaning participants are randomly assigned to one of the two treatments.

How Is the Trial Designed?

Group I: VNS Treatment Active Control 1 Intervention

Patients in the VNS treatment arm will undergo surgical VNS implantation.

Group II: DBS Treatment Active Control 1 Intervention

Patients in the DBS treatment arm will undergo surgical DBS implantation.

Who Is Running the Clinical Trial?

The Hospital for Sick Children

Lead Sponsor

Trials

724

Recruited

6,969,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11791334/

Effect of deep brain stimulation on the severity of seizures ... Two-year follow-up data showed a median seizure frequency reduction of 56 % and a response rate (patients exhibiting more significant than 50 % ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0920121125001081

Deep brain stimulation for epilepsy: A systematic review ... Results. Fourty-nine articles met the inclusion criteria. The mean seizure reduction (SR) across 21 studies was 62.31 % (95 % CI: 55.99 ...

3. europe.medtronic.com europe.medtronic.com/xd-en/healthcare-professionals/therapies-procedures/neurological/deep-brain-stimulation/indications/epilepsy/clinical-outcomes.html

CLINICAL OUTCOMES: EPILEPSY Deep Brain Stimulation EFFECTIVENESS RESULTS​​ DBS for Epilepsy was shown to reduce median seizure frequency, and these results improved over time. Our therapy benefits were consistent ...

4. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2023.1169105/full

Deep brain stimulation for patients with refractory epilepsy Results: Out of the 65 included patients, 46 (70.8%) responded to DBS. Among the 65 patients, 45 underwent ANT-DBS, 29 (64.4%) responded to the treatment, and ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11656455/

The Evolving Landscape of DBS in Epilepsy - PMC The study reported a median seizure reduction of over 60% at 5 years, whereas the MORE study, demonstrated a median seizure reduction of 56% ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40679272/

Cognitive outcomes after deep brain stimulation in drug- ... Both treatments effectively reduced seizures by over 70%. Importantly, after 2-4 years of continuous stimulation, neither treatment caused any ...

7. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf/P960009S478B.pdf

P960009/S478 Summary of Safety and Effectiveness (SSED) Medtronic's Deep Brain Stimulator (DBS) System was approved for the following indications for use: • P960009 approved on July 31, 1997: Unilateral thalamic ...

8. aesnet.org aesnet.org/abstractslisting/single-center-retrospective-analysis-of-epilepsy-surgery-outcomes-from-deep-brain-stimulation-therapy-for-epilepsy

Single-Center-Retrospective-Analysis-of-Epilepsy-Surgery ... Three patients have had DBS therapy for two years, and the average seizure reduction for these three patients at year two was 79.17%. There were ...